8-68476982-C-G

Position:

• chr8-68476982-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052958.4(C8orf34):​c.736+8162C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,898 control chromosomes in the GnomAD database, including 30,280 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30280 hom., cov: 32)
• Consequence: C8orf34 NM_052958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.947

Genes affected

C8orf34 (HGNC:30905): (chromosome 8 open reading frame 34) This gene encodes a protein that is related to the cyclic AMP dependent protein kinase regulators. Naturally occurring mutations in this gene are associated with an increased risk for severe toxicities, such as diarrhea and neutropenia, in patients undergoing chemotherapeutic treatment. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C8orf34	NM_052958.4	c.736+8162C>G		intron_variant		ENST00000518698.6	NP_443190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C8orf34	ENST00000518698.6	c.736+8162C>G		intron_variant		2	NM_052958.4	ENSP00000427820.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95257 AN: 151780 Hom.: 30265 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 95309 AN: 151898 Hom.: 30280 Cov.: 32 AF XY: 0.637 AC XY: 47298 AN XY: 74214

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.636

Alfa AF: 0.495 Hom.: 1397

Bravo AF: 0.619

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1517114; hg19: chr8-69389217;